关键词: 阿尔茨海默病, 冈田酸, 神经元微管蛋白相关蛋白, 神经原纤维缠结

Abstract: Objective To investigate the effect of okadaic acid (OA)-induced phosphorylation of neuron micro-tubule associated protein tau (Tau) on the damage of human neuroblastoma SH-SY5Y cells. Methods SH-SY5Y cells were incubated with different concentrations (20 and 40 nmol/L) of OA for 0, 12, 24, 48 and 72 hours followed by microscopy for cell morphology.Cell ultrastructure was observed by transmission electron microscope and cell apoptosis was detected by TUNEL assay. The protein expression of p-Tau and caspase3 was analyzed by Western blot and mRNA level of inhibitor of apoptosis family proteins (IAPs) was determined by RT-qPCR. Results OA induced phosphorylation of Tau protein in SH-SY5Y cells as compared to the result from control goup (P＜0.001), promoted cell damage and apoptosis (P＜0.001).OA also injured mitochondrial structure in a concentration and time dependent manner. It can also up-regulate IAPs expression significantly (P＜0.05). Conclusions The aberrant phosphorylation of Tau protein in SH-SY5Y cells induced by OA may lead to cell injury and apoptosis. Inhibition of endogenous apoptotic pathways or up-regulation of IAPs family proteins provides potential targets for AD prevention and treatment.

Key words: Alzheimer's disease, okadaic acid, Tau, neurofibrillary tangle